ABSTRACT: Cognitive Function, Alzheimer's Disease and Related Disorders (ADRD) in HAALSI The overarching goal of this study is to identify the incidence and prevalence of Alzheimer's Disease and Re- lated Dementias (ADRD) and associated biological and social risk factors in a population-based cohort of South African men and women aged 40 and over (n=5059) living in Agincourt, South Africa. The Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) has completed its first wave and continues for two additional waves through 2021, providing over 6 years of follow-up. HAALSI was developed as a harmonized sister study to the US Health and Retirement Study (HRS) and other global studies. In 2016, we launched the HAALSI Dementia Study, including all probable cases of dementia within HAALSI, and a subsample of HAALSI participants with normal cognition and mild cognitive impairment (MCI) for more detailed cognitive, clinical, and functional assessments (n= 607). The approach of the currently pro- posed extension of the HAALSI Dementia Study is to field two additional waves of enriched assessments sup- plemented with MRIs to obtain more detailed information on social and biological risk factors for ADRD in the HAALSI cohort. We will add new cases of probable dementia based on cognitive screening in future HAALSI waves to gather longitudinally accurate incidence and prevalence rates over 6 years. AIM 1: Estimate the incidence and prevalence of ADRD and characterize cognitive function and change in the HAALSI cohort. With 6 years of longitudinal information, we have 3 waves of sensitive neuropsycholog- ical measures, clinical and informant assessments, and functional outcomes. We estimate prevalent and inci- dent dementia cases and describe trajectories of cognitive aging, and describe structural markers of brain ag- ing via an MRI substudy. AIM 2: Evaluate biological predictors of incident dementia, cognitive function and decline, and brain aging. We use MRI to measure regional volume, cortical thickness, and markers of small and large vessel cerebrovascular disease. We assess associations between neuroimaging biomarkers, dementia, and cognitive impairment and associations with HIV and vascular disease. Venous blood collection enables us to evaluate known genetic risks for ADRD, such as Apolipoprotein E (APOE)-E4 allele, ATP- binding cassette sub-family A member 7 (ABCA7) and AD polygenic risk scores in this novel population. AIM 3: Evaluate social risks factors for incident dementia and cognitive impairment and decline. We will administer psychosocial measures to examine the extent to which dementia, cognitive decline, and brain func- tion are affected by educational experience, social engagement and networks, and childhood adversity. We will explore mediating relationships between biological and social risk factors on outcomes. Our study makes an important contribution to understanding ADRD, cognition, and brain aging in sub-Saharan Africa where many countries are experiencing rapid demographic and epidemiologic transitions.